In decision making concerning the diagnosis and treatment of patients, doctors have a responsibility to do this to the best of their abilities. Yet we argue that the current paradigm for best medical practice – evidence-based medicine (EBM) – does not always support this responsibility. EBM was developed to promote a more scientific approach to the practice of medicine. This includes the use of randomized controlled trials in the testing of new treatments and prophylactics and rule-based reasoning in clinical decision making. But critics of EBM claim that such a scientific approach does not always work in the clinic. In this article, we build on this critique and argue that rule-based reasoning and the use of general guidelines as promoted by EBM does not accommodate the complex reasoning of doctors in clinical decision making. Instead, we propose that a new medical epistemology is needed that accounts for complex reasoning styles in medical practice and at the same time maintains the quality usually associated with ‘scientific’. The medical epistemology we propose conforms to the epistemological responsibility of doctors, which involves a specific professional attitude and epistemological skills. Instead of deferring part of the professional responsibility to strict clinical guidelines, as EBM allows for, our alternative epistemology holds doctors accountable for epistemic considerations in clinical decision making towards the diagnosis and treatment plan of individual patients. One of the key intellectual challenges of doctors is the ability to bring together heterogeneous pieces of information to construct a coherent ‘picture’ of a specific patient. In the proposed epistemology, we consider this ‘picture’ as an epistemological tool that may then be employed in the diagnosis and treatment of a specific patient.